Anorexia nervosa (AN) and bulimia nervosa (BN) are eating disorders, from which 0.5 to 3.7% and 1.1-4.2% of female are suffered respectively over their lifetimes. It is said that the prevalence rate of eating disorders in male is about 10% of that in female. A majority of patients with eating disorders are female in puberty/adolescence, and a mentality desiring losing weight is quite noticeable. The number of patients with eating disorders in Japan has increased recently, and it has been found that the number of patients with eating disorders has been increased by about 10 times during 20 years from 1980. The prominent symptoms of anorexia nervosa are lack of food appetite, losing weight, amenorrhea, etc. and the anorexia nervosa is characterized by refusal of maintenance of the minimum standards of body weight. The prominent symptoms of bulimia nervosa are to have a behavior of frequently repeating overeating so-called “eating for diversion”, and an inadequate compensatory behavior such as vomiting or abusing laxatives just after overeating. As stated above, these two conditions looks like completely opposite diseases, but a patient with anorexia nervosa may show the symptoms of bulimia nervosa several months later, or on the other hand, a patient with bulimia nervosa often shows the symptoms of anorexia nervosa. Namely, anorexia nervosa and bulimia nervosa are not separate diseases, but diseases which may be shifted each other or overlapped each other, and patients with these conditions are extremely varied, and the disease states are also complicated. The cognitive impairment of body figure and body weight is an essential feature of anorexia nervosa and bulimia nervosa.
For example, serotonin acts on food intake regulation mechanism in the medial hypothalamic area, and particularly inhibits the intake of hydrocarbons. Patients with bulimia nervosa show a potent preference for high-energy food and take significantly increased amount of food at one time, which potently indicate the abnormality of serotonergic neurons. In eating disorders, it is observed that there is a breakdown of the controlling mechanism of eating not only in the brain but also at the peripheral level. Cholecystokinin is a peripheral signal transmitter of satiety, and transmitted into the neutral system via vagus nerve to stop food intake. It is observed in patients suffering from anorexia nervosa that the cholecystokinin overresponds to eating, and on the other hand, in bulimia nervosa, it is assumed that said response to eating disappears. It has also been confirmed in animal tests that the signal of cholecystokinin is transmitted to the central nervous system via serotonergic neurons, and it is pointed out that the transmitting process is possibly disturbed in association with abnormal function of serotonergic neurons.
The patients of anorexia nervosa and bulimia nervosa have various mental and physical disorders in addition to eating disorders. In order to clarify the causes, the dynamics of eating controlling material in cerebrospinal fluid and in blood has been studied. The dynamic change thereof occurs secondarily as a result of eating disorders in most cases and it is a limited case to show such a dynamic change.
For diagnosis of these anorexia nervosa and bulimia nervosa, various studies are reported with using blood or urine samples of the patients, but an established diagnostic method is not yet found. It has been desired to establish a comprehensive therapeutic system for early diagnosis, therapy, social rehabilitation and recurrence prevention in view of the specificity of the diseases. The treatment of eating disorders is done by drug therapy, cognitive behavior therapy, group behavior therapy, and the like. As the drug therapy, there are used antidepressants (cf. Masand P. S. et al., Selective serotonin-reuptake inhibitors; an update., Harvard Rev. Psychiatry (1997) 7: 69-84; and Kaye W. et al., Serotonin neuronal function and selective serotonin reuptake inhibitor treatment in anorexia and bulimia nervosa, Biol. Psychiatry (1998) 44: 825-38).
A brain-derived neurotrophic factor (hereinafter, referred to as “BDNF”) is one of neurotrophic factors which has been found in the brain and it is known that it plays an important role for formation and development of brain neural network and further maintenance of survival thereof. In later 1990s, it has been found that BDNF participants in synaptic plasticity and plays also an important role for memory and learning. It is further reported that it has a protecting activity against death of neurocyte. It has been indicated that chronic administration of an antidepressant such as serotonin uptake inhibitors induces increase of BDNF in hippocampus, and therefore it is suggested that there is a correlation between BDNF and serotonergic neurons. It is also suggested by recent study with a transgenic animal that BDNF also participates in eating behavior (cf. Lyons W. E. et al., Brain-derived neurotrophic factor-deficient mice develop aggressiveness and hyperphagia in conjunction with brain serotonergic abnormalities, Proc. Natl. Acad. Sci. USA (1999) 96: 15239-15244). However, there is no report of the role of BDNF in patients suffered from eating disorders.
As mentioned hereinabove, anorexia nervosa and bulimia nervosa have recently increased, but the symptoms thereof are, at a glance, contradictory states of disease and are various and complicated. Accordingly, it is very difficult to diagnose the disorders, which causes further deterioration of the symptoms. Thus, it has been desired in medical field to find improved diagnostic agent, diagnostic method, therapeutic agent and method for detection of therapeutic agent so that the eating disorders can be early diagnosed.